Indian researchers develop nanozymes that can block HIV reactivation
Bengaluru, Apr 1: Researchers at the Indian Institute of Science (IISc) here have developed artificial enzymes that they said can successfully block reactivation and replication of the Human Immunodeficiency Virus (HIV) in the host's immune cells.
Made from vanadium pentoxide nanosheets, these "nanozymes" work by mimicking a natural enzyme called glutathione peroxidase that helps reduce oxidative stress levels in the host's cells, which is required to keep the virus in check, an IISc statement said on Thursday.
The study, published in 'EMBO Molecular Medicine, was led by Amit Singh, Associate Professor and Wellcome Trust-DBT India Alliance Senior Fellow at the Department of Microbiology & Cell Biology and Centre for Infectious Diseases Research (CIDR), and Govindasamy Mugesh, Professor at the Department of Inorganic and Physical Chemistry.
"The advantage is that the nanozymes are stable inside biological systems and do not mediate any unwanted reactions inside the cells," Mugesh said. "They are also quite easy to prepare in the lab."
There is currently no way to eliminate HIV from a patient's body completely, according to the statement.
Anti-HIV drugs are only successful in suppressing the virus; they fail at eradicating HIV from infected cells. The virus hides inside the hosts immune cells in a "latent" state and stably maintains its reservoir.
When the levels of toxic molecules such as hydrogen peroxide increase in the host's cells, leading to a state of increased oxidative stress, the virus gets "reactivated" - it emerges from hiding and begins replicating again, it said.
A few years ago, Amit Singh's team developed a biosensor to measure oxidative stress levels in HIV-infected immune cells in real-time, it was stated.
"We found that to come out of latency and reactivate, HIV needs very little oxidative stress," he said.
One way to prevent reactivation is to keep the oxidative stress constantly low, which would "lock" the virus in a permanent state of latency.
Enzymes such as glutathione peroxidase are essential for this process; they convert toxic hydrogen peroxide to water and oxygen. However, inducing the host cells to produce more quantities of these enzymes could disrupt the tightly regulated cellular redox machinery.
Around the same time, Mugesh's group published a study showing that nanowires made of vanadium pentoxide can efficiently mimic the activity of glutathione peroxidase.
Singh's lab, therefore, decided to collaborate with them.
The researchers prepared ultrathin nanosheets of vanadium pentoxide in the lab and treated HIV-infected cells with them.
The sheets were found to reduce hydrogen peroxide just as effectively as the natural enzyme and prevent the virus from reactivating.
"We found that these nanosheets were having some sort of direct effect where the expression of the host genes essential for virus reactivation is reduced," said Shalini Singh, first author and Research Associate at CIDR.
When the team treated immune cells from HIV-infected patients undergoing antiretroviral therapy (ART) with the nanozymes,latency was induced faster and subsequent reactivation was suppressed when therapy was stopped, indicating that combining the two was more effective, she added.
Combining ART with the nanozymes also has other advantages.
Some ART drugs can cause oxidative stress as a side effect, which can damage heart or kidney cells, Amit Singh said.
"Adding a nanozyme like this can help in reducing the side effects caused by such ART drugs." This can improve the quality of life of HIV patients undergoing treatment.
Although the nanozymes were found to be harmless to normal cells in lab tests, Mugesh said further studies are needed to understand if they can have other effects once they are introduced inside the body.
"Where will they go? Which organs will they enter? How long will they stay in the body? We need to look at all these aspects," he added.
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Rishabh Pant's troubles continue as Punjab Kings push LSG towards exit door
Dharamsala, May 4 (PTI): Rishabh Pant lost the grip on his bat and the match simultaneously as Punjab Kings rode on heroics from the two 'Singhs' -- Prabhsimran and Arshdeep -- to literally push Lucknow Super Giants to the brink of elimination with a 37-run win in an IPL match here on Sunday.
It was Prabhsimran's 48-ball 91 that formed the cornerstone of Punjab Kings' unassailable 236 for 5 and any hopes of a remarkable chase was nipped in the bud by Arshdeep's (3/16 in 4 overs) now familiar Powerplay spell which summarily destroyed the opposition top-order.
This time, he got the three top run getters -- Mitchell Marsh (0), Aiden Markram (13) and the ever-dangerous Nicholas Pooran (6) -- to swing the match decisively in Punjab's favour. Ayush Badoni's (74 off 40 balls) effort was a good one albeit it came for a losing cause.
LSG were finally restricted to 199 for 7 in 20 overs and even if they win their last three games and get to 16 points from 14 games, their net run-rate can make things difficult for them.
Punjab Kings are now placed second with 15 points from 11 games and one more win could possibly clinch a place in top four for them.
But what is becoming an eyesore is LSG's Rs 27 crore worth skipper Pant's inexplicable approach which has fetched him a dismal 128 runs in 11 innings at a sub-100 strike-rate (99.22).
On the day, he scored 18 off 17 balls and that he is completely out of sync was evident in the manner he tried to throw the proverbial kitchen sink at an Azmatullah Omarzai delivery. There was no control in his shot as the bat took off on parabolic curve towards square leg and the ball went towards deep point.
Pant's misery was a testimony of LSG's wretched campaign that was lost at the auction table when the owner decided to go with a sub-standard bowling attack based on a half-fit talented pacer Mayank Yadav.
Mayank has already lost at least 10-15 yards of pace post rehabilitation under the watch of Nitin Patel at the National Cricket Academy.
On Sunday, he went for 60 runs off four overs with half a dozen of sixes struck off his bowling.
The pint-sized Prabhsimran packed a mean punch in his strokes as he blasted his way to a 48-ball 91 with the help of six fours and seven sixes.
The Punjab keeper-batter should have got his second IPL hundred but an ambitious switch hit off Digvesh Rathi saw him head back to the pavilion, nine runs short of what would have been a deserving milestone.
Towards the end, Shashank Singh scored 33 off 15 balls to take PBKS to what looked like an unassailable total. There were 16 sixes hit by Pujab Kings with 13 coming off pacers.
Prabhsimran was initially a passive partner as it was Australian Jos Inglis who launched the first attack with a hat-trick of sixes off Mayank Yadav, whose speed has decreased by at least 15 kmph post his intense rehab under Nitin Patel at the BCCI's erstwhile National Cricket Academy to recover from back injury.
However, once Inglis was dismissed, Prabhsimran, along with skipper Shreyas Iyer (45 off 25 balls), took control of the game. They were only helped by some atrocious fielding from Avesh Khan, who would probably go down as the worst fielder in the 18-year history of IPL.
Adding insult to injury, Prabhsimran took the tall MP fast bowler to the cleaners as he was pulled over mid-wicket for back-to-back maximums. Khan went for 57 in four overs and if around 15 runs due to his misfielding is added, he caused the maximum damage for his team.
The duo of Prabhsimran and Iyer added 78 runs in 7.5 overs before Rathi, LSG's best bowler on view, became the first spinner in the current season to account for Punjab Kings skipper's wicket.
But Prabhsimran continued like a man possessed and LSG bowlers were guilty of feeding to his strengths throughout the innings.
